Transient blood thinning during extracorporeal blood purification via the inactivation of coagulation factors by hydrogel microspheres

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Faith moves mountains.
Anticoagulation plays a fundamental role in clinical blood-purification procedures. Heparin is widely used to achieve systemic anticoagulation and to avoid clot formation. Thus, different anticoagulant molecules like heparin or antidotes like protamine have been developed to achieve sufficient anticoagulation without excessive bleeding risk. Since 1993, we have also reported published nearly hundreds of papers for various hemodialysis membranes or hemoperfusion adsorbents by coating, grafting, or blending heparin-like molecules. However, the side effects of these water-soluble molecules cannot be avoided while the success rate of heparin-mimetic materials was unsatisfactory, and we usually feel that we are doing some parallel work.
We started attempting to replace the anticoagulant medications with rationally designed materials. In 2017, we developed a promising approach utilizing superparamagnetic nano-anticoagulants for blood clotting prevention and then removing them before transfusing the blood back to body by an external magnetic field, thus avoiding the bleeding risks to certain content. However, it’s difficult to remove these nano-anticoagulants completely from the extracorporeal circuit, thereby remaining limitations of safety and efficacy, which is also the reason why our manuscript was rejected when we submitted it to Nature Biomedical Engineering. After that, we have made great efforts to develop an ideal anticoagulant system to significantly improve the safety and efficacy for extracorporeal blood purification. To prevent the anticoagulants from returning to the body within the bloodstream, we proposed a transient blood-thinning strategy whereby polymeric microspheres are placed into a cartridge to prevent blood clotting. These microspheres exhibited excellent anticoagulant properties but the mechanism underlying the anticoagulant properties remains unmet.

Interdisciplinary collaboration helps us view problems from a new perspective
When we communicated with a researcher with medical background at a conference in China, he asked me a question "Do you want to achieve a similar effect like hemophilia in extracorporeal circuit", which brought us a lot of inspiration. We quickly found out the experimental method of coagulation factors and carried out research on the coagulation factors. At the conference in Mauritius, we further communicated it with Prof. Jayachandran Kizhakkedathu and then reached an interdisciplinary collaboration. Finally, we cooperated with institute of blood transfusion in Peking Union Medical College, center for blood research and life science institute in University of British Columbia and department of nephrology in West China Hospital, and published this article jointly. We am sincerely thankful to our wonderful cooperators, students (Xin, Haifeng and Yupei), and Sichuan University. We anticipate that our strategy will not only provides safety and innovation in blood purification, but also be beneficial to extracorporeal membrane oxygenation (ECMO) treatment for patients with critical COVID-19. As the Coronavirus pandemic goes global, unity and cooperation are our most potent weapons to address these common threats and challenges.

Weifeng Zhao

Professor, Sichuan University